This is a pilot study (n=35 patients in total in two arms) testing the hypothesis that the inhibition of MEK can restore iodine incorporation in BRAF wild type (n=25 patients) and a combined inhibition of BRAF and MEK can restore iodine incorporation in BRAFV600E mutant (n=10 patients), radioiodine-refractory (RAIR) thyroid cancer.
- Conditions
- Radio Iodine Refractory Thyroid CancerTherapeutic area: Diseases [C] - Cancer [C04]
- Registration Number
- EUCTR2016-002941-49-DE
- Lead Sponsor
- niversity Hospital Essen (Anstalt des öffentlichen Rechts)
- Brief Summary
Not available
- Detailed Description
Not available
Recruitment & Eligibility
- Status
- Authorised-recruitment may be ongoing or finished
- Sex
- All
- Target Recruitment
- 35
•Patients must have histologically or cytologically confirmed progressive radioiodine refractory metastatic thyroid carcinoma of follicular origin (including papillary and its respective variants).
•Confirmation in a certified laboratory of the mutation status of BRAF gene (primary tumor, recurrent tumor, or metastasis) .
•Patients for whom a systemic treatment with sorafenib or lenvatinib or a chemotherapy is not considered and/or who refused to take either of these drugs within the next 6 months.
•Patients must have measurable disease, defined as at least one lesion that can be accurately measured in at least one dimension (longest diameter to be recorded for non-nodal lesions and short axis for nodal lesions) as = 15 mm with CT scan, MRI, or calipers by clinical exam. Tumors in previously irradiated fields may be considered measureable if there is evidence of tumor progression after radiation treatment.
•RAI-refractory disease on structural imaging, defined as any one of the following:
1) A metastatic lesion that is not radioiodine-avid on a diagnostic or therapeutic radioiodine scan performed less than 1 year prior to enrollment in the current study, or
2) Morphologically progressive or stable disease despite adequate RIT at least 6 month prior to enrollment in the current study
There are no size limitations for the index lesion used to satisfy this entry criterion.
•No recent treatment for thyroid cancer as defined as:
1)No prior 131I therapy is allowed < 6 months prior to initiation of therapy on this protocol. A diagnostic study using < 400 MBq of 131I is not considered 131I therapy.
2)No external beam radiation therapy < 4 weeks prior to initiation of therapy on this protocol. (Previous treatment with radiation for any indication is allowed if the investigator judges that the previous radiation does not significantly compromise patient safety on this protocol.)
3)No chemotherapy or targeted therapy (e.g., tyrosine kinase inhibitor) is allowed < 4 weeks prior to the initiation of therapy on this protocol.
•Age = 18 years.
•ECOG performance status = 2 (or Karnofsky =60%, see Appendix D).
•Life expectancy of greater than 3 months.
•Able to swallow and retain orally-administered medication and does not have any clinically significant gastrointestinal abnormalities that may alter absorption such as malabsorption syndrome or major resection of the stomach or bowels.
• All prior treatment-related toxicities must be CTCAE v4.0 grade = 1 (except alopecia). Grade 2 prior treatment related toxicities may be allowed after discussion with the Principal Investigator.
•Patients must have normal organ and bone marrow function as defined below:
•Absolute neutrophil count (ANC) > 1.5x109/L
•Hemoglobin = 9 g/dL
•Platelets = 100 x 109/L
•Albumin = 2.5 g/dL
•Total bilirubin = 1.5x institutional ULN
•Aspartate aminotransferase (AST) and alanine aminotransferase (ALT) = 2x institutional ULN unless it is related to the primary disease
•creatinine = 1.5 mg/dL OR calculated creatinine clearance (Cockcroft-Gault formula) = 50 mL/min OR 24-hour urine creatinine clearance = 50 mL/min
•Negative pregnancy test within 7 days prior to starting the study premenopausal women. Women of non-childbearing potential may be included without pregnancy test if they are either surgically sterile or have been postmenopausal for = 1 year.
•Fertile men and women must use an effective
•Concomitant malignancies or previous malignancies within the last 3 years. Exception: Patients who have been disease-free for 3 years, patients with a history of completely resected non-melanoma skin cancer, and/or patients with indolent secondary malignancies, are eligible.
•Use of other investigational drugs within 28 days preceding the first dose of drug treatment during this study.
•Symptomatic or untreated leptomeningeal or brain metastases or spinal cord compression.
•Have a known immediate or delayed hypersensitivity reaction or idiosyncrasy to drugs chemically related to trametinib and/or to dabrafenib .
•History or evidence of cardiovascular risk including any of the following:
•History or evidence of current, clinically significant uncontrolled arrhythmias (exception: patients with controlled atrial fibrillation for > 30 days prior to the initiation of therapy on this protocol are eligible).
•History of acute coronary syndromes (specifically, myocardial infarction and unstable angina), severe/unstable angina, coronary angioplasty, or stenting within 6 months prior to the initiation of therapy on this protocol.
•History of symptomatic congestive heart failure within 6 months prior to the initiation of therapy on this protocol.
•History of cerebrovascular attack or transient ischemic attack within 6 months prior to the initiation of therapy on this protocol.
•Uncontrolled intercurrent illness including, but not limited to, ongoing or active infection or psychiatric illness/social situations that would limit compliance with study requirements.
•Pregnant, lactating, or breast feeding women.
•Patients unable to follow a low iodine diet or requiring medication with high content in iodide (amiodarone).
•Patients who received iodinated intravenous contrast as part of a radiographic procedure within 3 months of study registration. Those that have had iodinated intravenous contrast within this time frame may still be eligible if a urinary iodine analysis reveals that the excess iodine has been adequately cleared after the last intravenous contrast administration.
•Unwillingness or inability to comply with study and follow-up procedures.
Study & Design
- Study Type
- Interventional clinical trial of medicinal product
- Study Design
- Not specified
- Primary Outcome Measures
Name Time Method
- Secondary Outcome Measures
Name Time Method